Positron Emission Tomography (PET) Study of Changes in [11C]AZ14132516 Uptake Following Administration of AZD7798 to Healthy Participants and Patients With Crohn's Disease

NCT06053424 | Completed Phase 1

• 1 other identifier: D9690C00004
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to measure the changes in small bowel uptake of radioligand \[11\^C\]AZ14132516 after intravenous (IV) administration of single and repeat doses of AZD7798 in healthy participants and participants with Crohn's disease. Study details include:

• The study duration will be variable (adaptive design).
• For Panels 1-5, there will be 5 in-person study visits: 1 screening visit, 1 visit for the baseline PET examination, 1 residential (24 hour) visit for AZD7798 administration and 2 visits for repeated PET examinations. There will be a final follow-up virtual visit (telephone call).
• For Panel 6, there will be 7 in-person study visits: 1 screening visit, 1 visit for the baseline PET examination, 2 residential (24 hour) visits for AZD7798 administration, 1 visit for pharmacokinetic (PK) blood sample and 2 visits for repeated PET examinations. There will be a final follow-up virtual visit.

Conditions

Crohn's Disease

Outcome Measures

Primary Outcomes (2)

• Percentage Change in Small Bowel Partition Coefficient (Kp) From Baseline (Positron Emission Tomography [PET]1 Visit) to PET2 Visit

  Kp is the partition coefficient that denotes radioactivity concentration ratio (area under the concentration-time curve \[AUC\] 0-60 min, intestines/AUC 0-60 min, blood). Kp denotes that denominator is the radioactivity measurement in blood (aorta), this is the reference region used in calculations. Percentage change in small bowel Kp from baseline (PET1 Visit) to PET2 visit is reported.

  PET1 visit (baseline; Day -7 to Day -1) and PET2 visit (Day 14 for all panels except Day 2 for Panel 3)

• Percentage Change in Small Bowel Kp From Baseline (PET1 Visit) to PET3 Visit

  Kp is the partition coefficient that denotes radioactivity concentration ratio (area under the concentration-time curve \[AUC\] 0-60 min, intestines/AUC 0-60 min, blood). Kp denotes that denominator is the radioactivity measurement in blood (aorta), this is the reference region used in calculations. Percentage change in small bowel Kp from baseline (PET1 Visit) to PET3 visit is reported.

  PET1 visit (baseline; Day -7 to Day -1) and PET3 visit (Day 42 for all panels except Days 56 and 28 for Panels 2 and 6, respectively)

Secondary Outcomes (17)

• Percentage Change From Baseline in Circulating C-C Chemokine Receptor Type 9 Positive (CCR9+) Memory T Cells in Panels 1 to 5

  Panels 1-5: Pre-dose (baseline) and 6 and 24 hours post-dose on Day 1, additionally; Panels 1, 4, and 5: Days 14 and 42; Panel 2: Day 14; Panel 3: Days 2 and 42

• Percentage Change From Baseline in Circulating CCR9+ Memory T Cells in Panel 6

  Pre-dose of Dose 1 (baseline), and 6 and 24 hours post-dose 1 on Day 1; pre-dose and 24 hours post-dose 2 on Day 15; and on Day 28

• Change From Baseline in C-C Chemokine Receptor Type 9 (CCR9) Receptor Occupancy as Free CCR9 on Total CCR9 Memory T cells in Blood in Panels 1 to 5

  Panels 1-5: Pre-dose (baseline) and 6 and 24 hours post-dose on Day 1, additionally; Panels 1, 4, and 5: Days 14 and 42; Panel 2: Day 14; Panel 3: Days 2 and 42

• Change From Baseline in CCR9 Receptor Occupancy as Free CCR9 on Total CCR9 Memory T cells in Blood in Panel 6

  Pre-dose of Dose 1 (baseline), and 6 and 24 hours post-dose 1 on Day 1; pre-dose and 24 hours post-dose 2 on Day 15; and on Day 28

• Serum Concentrations of AZD7798 in Panels 1 to 5

  Panels 1-5: Pre-dose, 1, 6, 24 hours post-dose on Day 1; additionally, Panels 1, 2, 4, and 5: Day 14; Panel 3: Day 2

Study Arms (6)

Panel 1

EXPERIMENTAL

Healthy participants will receive a single IV bolus dose of radioligand \[11\^C\]AZ14132516 between Day -7 to Day -1 followed by a single IV infusion of AZD7798 Dose Level 1 on Day 1. Thereafter, again will receive IV bolus dose of radioligand \[11\^C\]AZ14132516 on Day 14 and Day 42.

Drug: AZD7798; Drug: [11C]AZ14132516

Panel 2

EXPERIMENTAL

Healthy participants will receive a single IV bolus dose of radioligand \[11\^C\]AZ14132516 between Day -7 to Day -1 followed by a single IV infusion of AZD7798 Dose Level 2 on Day 1. Thereafter, again will receive IV bolus dose of radioligand \[11\^C\]AZ14132516 on Day 14 and Day 56.

Drug: AZD7798; Drug: [11C]AZ14132516

Panel 3

EXPERIMENTAL

Healthy participants will receive a single IV bolus dose of radioligand \[11\^C\]AZ14132516 between Day -7 to Day -1 followed by a single IV infusion of AZD7798 Dose Level 2 on Day 1. Thereafter, again will receive IV bolus dose of radioligand \[11\^C\]AZ14132516 on Day 2 and Day 42.

Drug: AZD7798; Drug: [11C]AZ14132516

Panel 4

EXPERIMENTAL

Participants with Crohn's disease will receive a single IV bolus dose of radioligand \[11\^C\]AZ14132516 between Day -7 to Day -1 followed by a single IV infusion of AZD7798 Dose Level 1 on Day 1. Thereafter, again will receive IV bolus dose of radioligand \[11\^C\]AZ14132516 on Day 14 and Day 42.

Drug: AZD7798; Drug: [11C]AZ14132516

Panel 5

EXPERIMENTAL

Participants with Crohn's disease will receive a single IV bolus dose of radioligand \[11\^C\]AZ14132516 between Day -7 to Day -1 followed by a single IV infusion of AZD7798 Dose Level 2 on Day 1. Thereafter, again will receive IV bolus dose of radioligand \[11\^C\]AZ14132516 on Day 14 and Day 42.

Drug: AZD7798; Drug: [11C]AZ14132516

Panel 6

EXPERIMENTAL

Participants with Crohn's disease will receive a single IV bolus dose of radioligand \[11\^C\]AZ14132516 between Day -7 to Day -1 followed by IV infusion of AZD7798 Dose Level 1 on Day 1 (Dose 1) and Day 15 (Dose 2). Thereafter, again will receive IV bolus dose of radioligand \[11\^C\]AZ14132516 on Day 14 and Day 28.

Drug: AZD7798; Drug: [11C]AZ14132516

Interventions

AZD7798 DRUG

Participants will receive IV infusion of AZD7798 as stated in arm description.

Panel 1; Panel 2; Panel 3; Panel 4; Panel 5; Panel 6

[11C]AZ14132516 DRUG

Participants will receive IV bolus dose of radioligand \[11\^C\]AZ14132516 as stated in arm description.

Panel 1; Panel 2; Panel 3; Panel 4; Panel 5; Panel 6

Eligibility Criteria

• Age: 20 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• HEALTHY PARTICIPANTS:
• Capable of giving signed informed consent as described in Appendix A which includes compliance with the requirements and restrictions listed in the informed consent form and in this protocol.
• Able and willing to participate in all scheduled evaluations, abide by all study restrictions, and complete all required tests and procedures.
• Participant must be ≥ 20 to 65 years of age inclusive, at the time of signing the informed consent.
• Type of Participant and Disease Characteristics
• Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory parameters, and cardiac monitoring before first administration of investigational product.
• Weight
• Body weight within 50.0 to 120.0 kg and body mass index within the range 18.0 to 35.0 kg/m\^2 (inclusive).
• Contraceptive use by males or females should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
• Male participants:
• Non-sterilized male participants who are sexually active with a female partner of childbearing potential must use a condom with spermicide during the study period and for at least 7 days following last radioligand administration and 4 months following last dose of AZD7798, whichever is longer.
• It is strongly recommended that female partners of male participants also use at least one highly effective method of contraception throughout this period.
• Male participants must refrain from fathering a child or donating sperm during the study period and for at least 7 days following last radioligand administration and 4 months following last dose of AZD7798, whichever is longer.
• Female participants:
• (i) Women of non-child bearing potential are defined as meeting one of the following criteria at screening:

You may not qualify if:

• HEALTHY PARTICIPANTS:
• Current significant major or unstable respiratory disease, heart disease, cerebrovascular disease, hematological disease, hepatic disease, renal disease, gastrointestinal disease, or other major disease.
• History of cancer with the following exceptions
• (a) Solid malignancy with curative therapy completed at least 5 years prior to screening (b) Basal cell carcinoma or localized squamous cell carcinoma of the skin or in-situ carcinoma of the cervix, provided that curative therapy was completed at least 12 months prior to screening
• History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity, as judged by the Investigator, or history of hypersensitivity to biologic therapies.
• Participants with unstable hypertension (as judged by the Investigator) or symptomatic hypotension, history of pre-syncope or syncope due to orthostatic hypotension and/or induced by change of posture (orthostatic hypotension defined as 25 mmHg decrease in systolic and/or 15 mmHg).
• Significant abnormalities on clinical examination, including neurological and physical examination, vital signs and electrocardiogram (ECG).
• Chemistry, hematology, or urine analysis results that may interfere with the study or present a safety risk to the participant.
• Leukocyte, lymphocyte, or neutrophil counts below the lower limit of normal. A re-test is allowed during screening in cases of mild leukopenia clinically suspected to be transient.
• Abnormal vital signs, after 10 minutes of supine rest as judged by the investigator. As a guide, any readings outside the following should be considered in the evaluation:
• Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG that may interfere with the interpretation of QTc interval changes. This may include participants with any of the following:
• PR (PQ) interval prolongation of clinical significance as judged by the Investigator
• Intermittent second or third-degree atrioventricular (AV) block (AV block II Mobitz type 1, Wenchebach, while asleep or in deep rest is not disqualifying)
• Incomplete, full, or intermittent bundle branch block (QRS ≤ 110 ms with normal QRS and T wave morphology is acceptable if there is no evidence of left ventricular hypertrophy)
• Abnormal T wave morphology

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (1)

Research Site

Stockholm, 14186, Sweden

Location

MeSH Terms

Conditions

Crohn Disease

Condition Hierarchy (Ancestors)

Inflammatory Bowel Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Study Officials

• Maria Creignou, MD

  Karolinska University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 30, 2023
• First Posted: September 25, 2023
• Study Start: September 25, 2023
• Primary Completion: October 8, 2024
• Study Completion: October 8, 2024
• Last Updated: August 27, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please refer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• Access Criteria: When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

Locations

SE (1)